This invention relates to potentiostat circuit(s) and related circuitry used for controlling the operation of an array of biosensors or other electrochemical sensors.
For over five million Americans with insulin-dependent diabetes (IDDM) there are tremendous personal, health and economic costs associated with maintaining normoglycemia to manage diabetes. These include careful monitoring of blood glucose levels, managing of food intake and activity, calculating insulin requirements and self-treating multiple times daily, either by injection or through infusion via an insulin pump. The risks of poor glucose control include the life-threatening crises that can occur due to severe hypoglycemia, and the long-term complications that result from hyperglycemia.
The use of continuous glucose monitoring (CGM) devices has been shown to improve blood glucose control and safely reduce hypoglycemia. There are a number of commercially available CGM devices currently in use by persons with diabetes. These devices are biosensors which are inserted through the skin and measure interstitial fluid glucose in subcutaneous tissue. The biosensors are used in conjunction with a conventional potentiostat.
FIG. 1 illustrates a conventional potentiostat circuit that operates a single sensor. FIG. 1 was reproduced from M. Ahmadi and G. Jullien, “A Very Low Power CMOS Potentiostat for Bioimplantable Applications,” Proc. 9th Intl. Database Engineering and Application Symposium (IDEAS '05), IEEE Computer Society, 2005. As shown in FIG. 1, the potentiostat circuit operates an electrochemical sensor (“Sensor Cell”) having three electrodes—(1) a working electrode (WE), (2) a reference electrode (RE), and (3) an auxiliary or counter electrode (CE). The potentiostat circuit of FIG. 1 has two basic functions. The first function is to maintain a specified (Vbias) potential between the working electrode and the reference electrode. The second function is to measure the working electrode current, which is sunk by the auxiliary electrode. The working electrode current is converted to a voltage using a transimpedance amplifier with feedback resistor RF.
Still referring to FIG. 1, the working electrode is maintained at a virtual circuit ground by way of the transimpedance amplifier. A control loop is established by comparing the reference electrode potential against a set point, Vbias, which is referenced to ground. The loop control amplifier drives the counter electrode to maintain the working electrode-to-reference electrode potential difference, Vcell, equal to Vbias.
FIG. 2 illustrates another conventional potentiostat that operates a single sensor in the form of an electrochemical cell. In particular, FIG. 2 shows an equivalent circuit for the electrochemical cell. In FIG. 2, the reference electrode is directly connected to the inverting input of the control amplifier, the set point voltage is applied to the noninverting input, and the auxiliary electrode is placed at its output. Rr is the reference electrode impedance, RC is the compensated resistance, Ru is the uncompensated resistance. As in FIG. 1, the working electrode is maintained at virtual circuit ground by feedback around the transimpedance amplifier. The output of this amplifier, E0, is directly proportional to the working electrode current, i, and is equal to the product of the current and the current-measuring resistor Rm, E0=−i*Rm. However, unlike FIG. 1, the cell voltage Vcell (working to reference electrode) is not equal to the set point voltage, Vbias. Instead, in FIG. 2, the cell voltage is the negative of the input voltage—that is, Vcell=−Ei. FIG. 2 has been reproduced from FIG. 6.7(b) of Kissinger, Lab Techniques in Electroanalytical Chemistry, Marcel Dekker Inc. 1984.
FIG. 3 illustrates another conventional potentiostat that operates a single sensor. In FIG. 3, the current measurement circuitry (I/E converter) is not part of the potential control loop since it is not required to maintain the working electrode (Wrk) at a specified potential. The sensor current is measured by inserting a sense resistor between the working electrode and the potentiostat's circuit ground. Both inputs of the I/E converter must be at high impedance if small currents are to be measured across the sense resistor Rm. Unlike FIG. 1, the working electrode is not at virtual ground. The working electrode voltage (relative to the potentiostat's ground) depends on the current flowing and will be at (i*Rm) volts. Because the working electrode is not at virtual ground, there is a differential amplifier/electrometer to measure the working to reference electrode potential difference. The arrow denoted “Wrk Sense” indicates the input from the working electrode. The differential amplifier/electrometer output is fed back to a summing junction of the control amplifier where it is summed with the desired working to reference electrode potential.
The Computer Retrieval of Information on Scientific Projects (CRISP) includes a 2005 abstract of Grant No. 5R44DK054545-03, entitled “Micropower Potentiostat for Implantable Glucose Sensors,” that was issued to Glysens, Inc (hereinafter “Glysens”). In the CRISP abstract, Glysens discloses it “previously developed an implantable glucose sensor based on immobilized glucose oxidase coupled to an oxygen electrode and employed the sensor as an intravenous implant for over 100 days in dogs without recalibration.” In addition, Glysens discloses “a Phase II effort to complete the development of novel micropower potentiostat instrumentation, principally for the implantable glucose sensor, but that may also find application with other implantable sensors and devices.”
It would be desirable to provide an improved continuous monitoring device that contains an array of sensors that can be operated sequentially to extend the life of the device (or monitor) well beyond the operating life of an individual sensor. In addition, it would be desirable to improve the precision and reliability of the measurement by operating more than one sensor simultaneously.